ABSTRACT Whole genome sequencing has vast potential to improve the care of generally healthy adults by identifying predispositions for disease to facilitate targeted prevention and screening efforts, by informing treatment options when illnesses do develop, and more. It may also cause more harm than good through false-positive findings, through unnecessary monitoring because of incomplete genetic penetrance, and because the conditions identified by genomic sequencing may lack effective prevention options. Adding to the unease about genomic sequencing are concerns that its use among healthy adults will cause healthcare expenditures to surge not only due to the costs of sequencing, variant classification, and periodic re-analysis, but also by initiating a cascade of follow-up diagnostic testing and potentially-unnecessary screening. Uncertainties about the utility and costs of integrating genomic sequencing into clinical settings are hindering the development of genomic testing policies and discouraging payers from reimbursing for these services, particularly for testing of populations that are asymptomatic for disease. Reservations about embracing genomic testing may be warranted, but are currently based in speculation about the benefits, harms and costs of sequencing rather than evidence. For the field of genomics to achieve its potential now and in the future, research programs need to begin systematically assessing these outcomes with rigor. This career development grant addresses the dearth of cost-effectiveness researchers in genomics by proposing a research and training agenda that builds on the recognized skills of a young outcomes researcher in clinical genomics to help him launch an independent career investigating the cost-effectiveness of genomic sequencing. Already, the candidate is a high-profile researcher, having received an NIH-funded National Research Service Award and having published over two dozen peer-reviewed publications about psychological and behavioral responses to genomic information. Through this grant, this newly-appointed Instructor will gain additional skills in cost- effectiveness research alongside clinical trials by conducting a five-year follow-up of the healthcare costs and health outcomes from his proposed mentor's pioneering randomized trial of whole genome sequencing in the clinical care of healthy adults, the MedSeq Project. The candidate will also gain skills in decision modeling and working with ?big data? by creating a decision-analytic model that projects the costs and utility of genomic sequencing over patients' lifetimes. Lastly, the candidate will identify the areas of research that will provide the most value for cost-effectiveness research by conducting a value-of-information analysis about genomic sequencing among healthy adults. Findings from the proposed research will not only generate critically-needed insight about the value of genomic sequencing among healthy adults, but will also provide the candidate with foundational skills and pilot data for an R01 submission to understand the cost-effectiveness of genomic sequencing throughout patients' lives.